the maturation time is used by making "abortive" or "futile" interactions until enough interactions occur simultaneously to allow the structure to continue to develop. The last step in the formation of a transport vesicle is "pinching off" from the donor membrane. This requires energy, but even in the well studied case of CCVs, not all require dynamin. The accompanying illustration shows the case for AP-2 CCVs, however AP-1 and AP-3 CCVs do not use dynamin. Selection of cargo molecules Which cargo molecules are incorporated into a particular type of vesicle relies on specific interactions. Some of these interactions are directly with AP complexes and some are indirectly with "alternative adaptors", as shown in this diagram. As examples, membrane proteins can have direct interactions, while proteins that are soluble in the lumen of the donor organelle bind indirectly to AP complexes by binding to membrane proteins that traverse the membrane and bind at their lumenal end to the desired cargo molecule. Molecules that should not be included in the vesicle appear to be excluded by "molecular crowding". The "signals" or amino acid "motifs" in the cargo proteins that interact with the adaptor proteins can be very short. For example, one well-known example is the dileucine motif, in which a leucine amino acid (aa) residue is followed immediately by another leucine or isoleucine residue. An even simpler example is the tyrosine based signal, which is YxxØ (a tyrosine residue separated by 2 aa residues from another bulky, hydrophobic aa residue). The accompanying figure shows how a small part of a protein can interact specifically with another protein, so these short signalling motifs should not be surprising. The sort of sequence comparisons used, in part, to define these motifs. In some cases, post-translational modifications, such as phosphorylations (shown in the figure) are important for cargo recognition. Diseases Adaptor diseases have been reviewed. AP-2/CCVs are involved in autosomal recessive hypercholesterolemia through the associated low-density lipoprotein receptor adapter protein 1. Retromer is involved in recycling components of the plasma membrane. The importance of that recycling at a synapse is hinted at in one of the figures in the gallery. There are at least 3 ways in which retromer dysfunction can contribute to brain disorders, including Alzheimer and Parkinson diseases. AP-5 is the most recently described complex, and one reason supporting the idea that it is an authentic adaptor complex is that it is associated with